The ion transport of the short-circuited rabbit corneal epithelium in vitro is due to inward (tear film to aqueous humor) active Na transport and to outward active Cl transport. Cyclic AMP mediates the Cl transport and causes outward NaCl movement in the presence of corneal resting potential. The objectives of the proposed research are to examine the relationship of these and other transport mechanisms to epithelial and stromal hydration; to examine the means and mechanisms by which epithelial permeability and transport are controlled; to examine the relative importance of transcellular versus extracellular pathways in ion and non-electrolyte transport; to determine the effect of denervation and neuroparalytic diseases on epithelial transport; and to correlate in vitro measurements with in vivo values. The primary in vitro approaches will include the voltage clamp technique, radioisotopic flux measurements, and corneal thickness measurements. These will be complemented by microelectrode techniques and electron microscopic observations. In this way it is hoped to approach an explanation, at the cellular level, of the mechanism by which the epithelium maintains its hydration and influences that of the stroma.